During two tularaemia outbreaks in the Bursa region of Turkey in 1991, a total of 98 patients were diagnosed and evaluated. Thirteen of these patients had erythema nodosum, which is accepted as a secondary skin manifestation. The patients with erythema nodosum, 21 patients without any skin lesions, and 20 healthy controls were studied. Comparable elevations of levels of IgG, IgA, and IgM were detected in the two tularaemia groups. There was no difference in complement C3c and C4 levels between the groups. All of the patients with erythema nodosum had elevated circulating immune complex (CIC) levels, when compared with the patients without skin lesions and the control group. The acute phase response (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) of the erythema nodosum group was significantly higher than the patients with normal skin, and healthy controls (P < 0.001). Serum transferrin levels were significantly decreased in both of the tularaemia groups (P < 0.001). Serum soluble interleukin-2 receptor levels (SIL-2R) were significantly elevated in both tularaemia groups (P < 0.001), and the elevation was more marked in the erythema nodosum group (P < 0.05). Histopathological evaluation of biopsies from two patients with erythema nodosum showed dermal oedema, a perivascular lymphocytic infiltrate, and panniculitis. No immunoglobulin or complement deposits were detected on immunofluorescence. Erythema nodosum in the course of tularaemia is associated with many immunological changes, although it is not clear whether these findings are related to the increased tissue response, or whether they play a role in the pathogenesis of the erythema nodosum.